Hydrogen Bond Energy Research Articles

Synthesis, spectral, structural and antimicrobial activities of Ethyl-4-｛[-(1-(2-(4-nitrobenzoyl)hydrazono)ethyl]｝-3,5-dimethyl-1H-pyrrole-2-carboxylate

A new ethyl-4-{[-(1-(2-(4-nitrobenzoyl)hydrazono)ethyl]}-3,5-dimethyl-1H-pyrrole-2-carboxylate (ENBHEDPC) has been synthesized, characterized (FT-IR, 1H and 13C NMR, UV-Visible, DART-Mass spectroscopy, elemental analysis) and evaluated for antituberculosis and antibacterial activity. Quantum chemical calculations have been performed by DFT level of theory using the B3LYP functional and 6–311++G(d,p) as basis set. The 1H and 13C NMR chemical shifts and electronic transitions are calculated using gage including atomic orbitals (GIAO) and time dependent density functional theory (TD-DFT) approach in DMSO as solvent. Combined theoretical and experimental wavenumber analyses confirm the existence of dimer. Hydrogen bonding and other multiple interactions have been analyzed by Bader's ‘Atoms in molecules’ AIM theory in detail. The intermolecular hydrogen bond energy of dimer is calculated as -12.28 kcal/mol. The calculated thermodynamic parameters show that reaction is exothermic and non-spontaneous at room temperature. The local reactivity descriptors analyses determine the reactive sites within molecule by nucleophilic attack. Nonlinear optical (NLO) behavior of title compound is investigated by the computed value of the first hyperpolarizability (β0). The synthesized compound show good antimicrobial and antituberculosis activity.

Study on the association driving force of low temperature coal tar asphaltenes

The aggregation of petroleum asphaltenes has been studied for decades by numerous experimental techniques, however, few studies had been performed on the special supramolecular structure of coal tar asphaltenes. In this paper, the methylation, alkylation experiments and molecular dynamics simulation were used to study the π-π interaction and hydrogen bond between coal tar asphaltenes. The results showed that the inter aromatic layer distance (Me) of asphaltenes, methylated and alkylated asphaltenes were 3.74, 2.12 and 1.73 respectively, and the average number of aromatic sheets (dm) was increased compared with asphaltenes. Asphaltenes existed in the form of aggregates in the toluene, as the concentration increased, the particle size also increased significantly, moreover, the particle size and the Me of alkylated asphaltenes are significantly less than asphaltenes, indicating that the π-π interaction was the main driving force for asphaltene association. Meanwhile, molecular simulation results showed the π-π interaction energy of asphaltenes dimers was -165.269 kcal·mol−1, which was much larger than the hydrogen bond energy -5.807 kcal·mol−1. In addition, the asphaltenes dimer layer spacing in quinoline, toluene and ethanol were 3.836 Å, 2.57 Å, and 4.783 Å respectively, which were all larger than the interlayer spacing of asphaltenes dimer 1.99 Å, and the asphaltenes dimer had a better disaggregates effect in quinolone.

Molecular Docking as a Tool to Examine Organic Cation Sorption to Organic Matter.

Molecular docking simulations were performed to examine the structural effects of organic cations on their sorption to organic matter. A set of benzylamine compounds was used to assess the sorption trends arising from the systematic structural differences between ring or nitrogen substituents. Binding simulations were performed using AutoDock 4.2 with Schulten's proposed soil organic matter as a representative organic matter structure. The calculated binding energies for the sorbate compounds correlated strongly with the measured sorption energies for Pahokee peat, indicating that the simulated binding energies and their associated sorbate orientations were representative of the experimental conditions. Graphical docking orientations showed primary, secondary, and tertiary aminium compounds to form hydrogen-bond interactions with deprotonated carboxylic acid groups in a pocket of the organic matter structure. Quaternary ammonium compounds formed pi-pi or cation-pi interactions with the aromatic groups elsewhere in the same organic matter pocket. Ring substituents showed no clear trends in sorption energies with the substituent group type for primary aminium compounds. Rather, substituent groups altered the simulated van der Waals, electrostatic, hydrogen-bond, and desolvation energy contributions to the overall sorption energies, in part because of the variations in docking orientations between compounds. Increasing methyl substitution of the aminium nitrogen group was associated with an increase in van der Waals energy contributions and a decrease in electrostatic energy contributions to the overall compound sorption energies because of aminium charge delocalization into methyl substituents and steric hindrance from methyl substituents to form specific interactions. The findings illustrate how molecular docking can be used to explore the effects of organic cation structure on sorption interactions with organic matter.

HYDROGEN BOND IN POTENTIALLY MESOGENIC MOLECULAR COMPLEXES OF 4-(PHENYLAZO)BENZOIC ACID AND 4-(PHENYLAZO)PHENOL WITH PYRIDINE DERIVATIVES

Using experimental and theoretical methods, it has been shown that hydrogen-bonded molecular complexes in two-component systems based on 4-pyridyl-4'-n-alkyloxybenzoates (n = 7, 12) with 4-(phenylazo)benzoic acid and 4-(phenylazo)phenol (composition of 1:1) are formed. Quantum chemistry methods (DFT (B3LYP)/cc-pVTZ) were used to determine the conformational properties of 4-(phenylazo)benzoic acid and 4-(phenylazo)phenol molecules. It has been shown that the introduction of 4-carboxy and 4-hydroxy groups into the azobenzene molecule has practically no effect on the energy characteristics of the trans-cis isomerization process. The energy, geometric, and electronic characteristics of intermolecular hydrogen bonds in the H-complexes have been estimated. The calculations showed that the H-complexes of 4-pyridyl-4-n-propyloxybenzoate with 4-(phenylazo)benzoic acid and 4-(phenylazo)phenol differ significantly from each other in geometric structure: the complex with 4-(phenylazo)benzoic acid – rod-shaped, complex with 4-(phenylazo)phenol – angular. A comparison of the energy characteristics of H-complexes, as well as the characteristics of hydrogen bonds, showed that a stronger hydrogen bond is formed in the complex with 4-(phenylazo)benzoic acid than in the complex with 4-(phenylazo)phenol. The results of modeling dimers of molecules of 4-(phenylazo)benzoic acid, 4-(phenylazo)phenol, reproducing intermolecular interactions in crystals, and their hydrogen-bonded complexes allow to conclude that in the process of self-organization of systems with a composition of 1:1, associates of 4-(phenylazo)benzoic acid molecules, associates of 4-(phenylazo)phenol molecules will be broken and H-complexes with 4-pyridyl-4'-alkyloxybenzoates will be formed instead. Changes in the experimental IR spectra recorded for the initial components and for systems with a composition of 1:1 confirm the formation of molecular complexes. The structural units of the studied systems based on 4-pyridyl-4'-alkyloxybenzoates with 4-(phenylazo)benzoic acid and 4-(phenylazo)phenol with a composition of 1:1 can be considered supramolecules, formed by hydrogen bonding. The structure of supermolecules and the presence of their geometric anisotropy indicate their potential mesogenicity. The sample of H-complexes of 4-(phenylazo)phenol and 4-pyridyl-4'-n-dodecyloxybenzoate (composition of 1:1) was studied for the manifestation of mesomorphic properties using the method of polarization thermomicroscopy. The textures registered in a polarizing microscope allow to conclude that the H-complex has a smectic mesophase in the temperature range of 101.4–109.4 °C.

Hydrogen bonding in the crystal of 1,1'-((1E,1'E)-(pyridine-3,4-diylbis(azanylylidene))bis(methanylylidene))-bis(naphthalen-2-ol) acetonitrile solvate: combined experimental and theoretical study

The title compound, 1,1'-((1E,1'E)-(pyridine-3,4-diylbis(azanylylidene))bis(methanylylidene))­bis(naphthalen-2-ol) (1), was synthesized and structurally characterized. The compound cocrystallized with one MeCN molecule. Interestingly, one of two salicylaldehyde Schiff base fragments exists in enol form, while the other one — in a ketone form. Moreover, cocrystallized acetonitrile molecule forms hydrogen bonding with three hydrogen atoms of the dye molecule. The nature and energies of intermolecular and intramolecular hydrogen bonds were studied theoretically using DFT calculations and topological analysis of the electron density distribution within the formalism of Bader's theory (QTAIM method).

Factors influencing hydrogen peroxide versus water inclusion in molecular crystals.

Hydrate formation is often unavoidable during crystallization, leading to performance degradation of pharmaceuticals and energetics. In some cases, water molecules trapped within crystal lattices can be substituted for hydrogen peroxide, improving the solubility of drugs and detonation performance of explosives. The present work compares hydrates and hydrogen peroxide solvates in two ways: (1) analyzing structural motifs present in crystal structures accessed from the Cambridge Structural Database and (2) developing potential energy surfaces for water and hydrogen peroxide interacting with functional groups of interest at geometries relevant to the solid state. By elucidating fundamental differences in local interactions that can be formed with molecules of hydrogen peroxide and/or water, the analyses presented here provide a foundation for the design and selection of candidate molecules for the formation of hydrogen peroxide solvates.

Reduced nucleophilicity: an intrinsic property of the Lewis base atom interacting with H in hydrogen-bonds with Lewis acids HX (X = F, Cl, Br, I, CN, CCH, CP)

Equilibrium hydrogen-bond dissociation energies De for the process B⋯HX = B + HX are calculated at the CCSD(T)(F12c)/cc-pVDZ-F12 level for ∼190 complexes B⋯HX. As established earlier, De values for such complexes can be described by the equation De = cNBEA, in which NB and EHX are the nucleophilicity and electrophilicity of the Lewis base B and the Lewis acid HX, respectively, and the constant c = 1 kJ mol-1. Graphs of De as the ordinate and EHX as the abscissa are presented for 26 series of hydrogen-bonded complexes B⋯HX. The Lewis base is fixed and HX is HF, HCl, HBr, HI, HCN, HCCH and HCP in each series. Each plot yields a good straight line, the slope of which is the nucleophilicity NB of B. The Lewis bases are chosen for their simplicity and all have at least one non-bonding electron pair carried by the atom directly involved in the B⋯HX hydrogen bond. The direction of the minimum value σmin of the molecular electrostatic surface potential on the 0.001 e bohr-3 iso-surface in the chosen bases B usually coincides with the axis of a non-bonding electron pair. The gradient of a graph of De/σmin plotted against EHX defines a reduced nucleophilicity ИB = NB/σmin in the sense that ИB appears to be a property only of the atom of B that is directly involved in the B⋯HX hydrogen bond, independent of the remainder of B. For example, the values of the reduced nucleophilicity for the series of isocyanide complexes CH3NC⋯HX, HNC⋯HX and FNC⋯HX are 0.0343(16), 0.0337(18) and 0.0332(18), respectively, while those for the corresponding series of cyanide complexes are 0.0337(23), 0.0329(24) and 0.0333(23).

Hydration shell model for expeditious and reliable individual hydrogen bond energies in large water clusters.

Recently, we have developed and tested a method, based on the molecular tailoring approach (MTA-based) to directly estimate the individual hydrogen bond (HB) energies in molecular clusters. Application of this MTA-based method to large molecular clusters is prohibitively difficult due to the evaluation of the energy of large-sized fragments. We propose here a smaller model system called the shell model, to overcome this difficulty. The shell model represents the first hydration shell of water molecules involved in the formation of HB under consideration. Utilizing the shell model as a parent system, fragmentation is carried out, in a fashion similar to the actual MTA-based method, to estimate individual HB energies in large water clusters (Wn, n = 10-16, 18 and 20). The estimated individual HB energies in these Wn clusters, employing the shell model, fall between 0.2 and 12.5 kcal mol-1 at the MP2/aug-cc-pVTZ level, with no net loss in the cooperativity contribution. We have also applied this shell model-based approach to estimate individual HB energies in the two lowest energy conformers of ammonia octamers (NH3)8 and mixed hydrogen fluoride-water clusters. The estimated individual HB energies employing the shell model, in all these molecular clusters studied in this work, are in good agreement with their actual MTA-based counterparts. The typical difference is less than 1 kcal mol-1. Importantly, the shell model has a huge computational time advantage over the actual MTA-based method and it requires only modest hardware.

Hydrogen Bond Energies in Formation of Water Molecule Clusters

During the last decades, the interest in water structure has increased as an important theoretical and practical problem, connected with different industrial and biological applications. Theoretically, the mechanisms of water molecules cluster formation have been of special interest. It has been assumed that aggregation of water molecules depends on the energy of hydrogen bonds. The character of this process was investigated in the present study. The approach was based on measurements of the wetting angle θ of water droplets at different energy levels during their evaporation. Taking into account previous findings that θ depends on the average energy of hydrogen bonds between water molecules, it was assumed that the size of water clusters is related to the value of θ, measured at different energy levels. This assumption was confirmed by the obtained experimental results.

Interaction Types in C6H5(CH2)nOH-CO2 (n = 0-4) Determined by the Length of the Side Alkyl Chain.

C6H5(CH2)nOH-CO2 complexes have been investigated using rotational spectroscopy (n = 0-2) complemented by quantum chemical calculations (n = 0-4), which implies that the side alkyl chain length can determine the types of intermolecular interactions. Unlike the in-plane C···O tetrel bond in phenol-CO2, the π*CO2···πaromatic interaction has been shown to link CO2 to phenylmethanol and 2-phenylethanol, which is, to the best of our knowledge, the first time it has been demonstrated by rotational spectroscopy. Further elongations of the side alkyl chain gradually increase the energies of intramolecular hydrogen bonds in 3-phenylpropanol and 4-phenylbutanol so that CO2 cannot break it. CO2 will be pushed farther from the monomers and link with the -OH group through a dominating C···O tetrel bond. Our observations would allow, with the choice of the proper length of the side alkyl chain, new strategies for engineering C···πaromatic-centered noncovalent bonding schemes for the capture, utilization, and storage of CO2.

Ranked binding energies of residues and data fusion to identify the active and selective pyrimidine-based Janus kinases 3 (JAK3) inhibitors

ABSTRACT The idea of using ranked binding energies of residues and data fusion are presented here for the first time as a valuable tool to classify active and selective inhibitors. Selective inhibitors of JAK3 can inhibit inflammatory cytokine while preventing targeting other subtypes of JAK1 and JAK2. Herein, we report a novel way to identify both active JAK3 and selective JAK1/JAK3 and JAK2/JAK3 inhibitors using the effective activity and selectivity classifications. The most important residues (top 10) responsible for the inhibition mechanism are sorted from high to low energies, which are considered as variables in the classification process. In addition, the ranked energies of ligands’ heteroatoms (top 5), ranked energies of hydrogen bonds (top 5) and important molecular descriptors (top 10) were used to construct different data fusion possibilities. It is shown that the proposed data fusion strategy can increase the accuracy of the activity classification to 100% and the selectivity classification to 96.4%. The proposed strategies represented in this paper can help medicinal or pharmaceutical chemist in evaluation of both active and selective inhibitors before synthesizing new pharmaceuticals.

ТЕРМОДИНАМИЧЕСКИЙ АНАЛИЗ ПРОЦЕССОВ ГИДРАТАЦИИ АЛЮМОФЕРРИТА КАЛЬЦИЯ

The processes of hydration and hydrate phase formation of calcium aluminoferrites are insufficiently covered in the technical literature. Thermodynamic analysis of the hydration processes of calcium aluminoferrite of 4CaO·Al2O3·Fe2O3 is difficult due to the unreliability of the initial data for hydration products. The question of the basicity of calcium hydroferrites requires clarification. There is insufficient data on the justification of the method of calculating the thermodynamic properties of hydroferrite -∆G0298, - ∆H0298 and c(T), verification of their results, the mechanism of formation of the complex anion Fe(OH)4- and its stability in the liquid phase of hydrating C4AF.
 The hydration of 4CaO·Al2O3·Fe2O3 with the formation of 2CaO·Al2O3·8H2O as hydrate phases is considered. The energy of hydrogen bonds between the layers of Ca(OH)2, Al2(OH)3 and Fe(OH)3, from which the hexagonal layers of these complex calcium, aluminum and iron hydroxides are composed, is compared. It is shown that the values of ∆G0298 and ∆H0298 2CaO·Fe2O3·8H2O, which are equal to -937.2 and -1082.3 kcal/mol, respectively, are not consistent with experimental data on the solubility of C2FH8 and the specific heat release during C4AF hydration (100-115 kcal/g). Values for C2FH8, ∆G0298= -933, ∆H0298 = -1072 kcal/mol are recommended. It is shown that the formation of Fe(OH)3 hydroxide in the amorphous state, rather than the Fe(OH)4 ion, is preferable as an intermediate product of C4AF hydration.

Elucidating the Supramolecular Copolymerization of N- and C-Centered Benzene-1,3,5-Tricarboxamides: The Role of Parallel and Antiparallel Packing of Amide Groups in the Copolymer Microstructure.

An in‐depth study of the supramolecular copolymerization behavior of N‐ and C‐centered benzene‐1,3,5‐tricarboxamides (N‐ and C‐BTAs) has been conducted in methylcyclohexane and in the solid state. The connectivity of the amide groups in the BTAs differs, and mixing N‐ and C‐BTAs results in supramolecular copolymers with a blocky microstructure in solution. The blocky microstructure results from the formation of weaker and less organized, antiparallel hydrogen bonds between N‐ and C‐BTAs. In methylcyclohexane, the helical threefold hydrogen‐bonding network present in C‐ and N‐BTAs is retained in the mixtures. In the solid state, in contrast, the hydrogen bonds of pure BTAs as well as their mixtures organize in a sheet‐like pattern, and in the mixtures long‐range order is lost. Drop‐casting to kinetically trap the solution microstructures shows that C‐BTAs retain the helical hydrogen bonds, but N‐BTAs immediately adopt the sheet‐like pattern, a direct consequence of the lower stabilization energy of the helical hydrogen bonds. In the copolymers, the stability of the helical aggregates depends on the copolymer composition, and helical aggregates are only preserved when a high amount of C‐BTAs is present. The method outlined here is generally applicable to elucidate the copolymerization behavior of supramolecular monomers both in solution as well as in the solid state.

In Silico Studies of Bioactive Compounds from Hibiscus rosa-sinensis Against HER2 and ESR1 for Breast Cancer Treatment

The most common type of cancer and the second biggest cause of death is breast cancer. The disease is the leading cause of death in women aged 45 to 55. It's a multi-stage disease in which viruses have a role in one stage. Breast cancer is an illness that affects the sufferer, their family, and the entire community all over the world. Breast cancer has no established cause, however specific risk factors have been found. Age, race, gender, and family history are all fixed and immutable characteristics. Other elements, such as social and familial support, can help to mitigate the harmful effects.The aim of the present study was to investigate the bioactive ligand for the breast cancer treatment against the HER2 and ESR1 proteins by molecular docking studies. HER2 is an oncogene and membrane tyrosine kinase that is overexpressed and gene amplified in about 20% of breast tumours. When active, it sends proliferative and anti-apoptotic signals to the cell. It is the most important factor in the genesis and progression of breast cancer tumours. To carry out this work protein structures were download from the PDB database and ligands three dimensional structures were downloaded from the PubChem database. The docking was performed by using the iGEMDOCK software suit. The binding energies of bioactive molecules from Hibiscus rosa-sinensis were found to be Rutin (-139.779, -102.743), Quercetin (-106.5, -99.7807), Kaempferol (-105.824, -92.5271), Myricetin (-111.913, -99.603) and Methotrexate (-140.69, -130.165) against HER2 and ESR1 proteins respectively. Lowest energy of Rutin compared to Methotrexate showed highest binding among the other bioactive molecules.The binding energies of the molecules are the sum of hydrogen bond, vanderwaal’s and electrostatic energies that inversely linked to protein-ligand interaction. From the result of the current study we can conclude that among the four bioactive molecule rutin has lowest binding energy so it could be used as an inhibitor of HER2 and ESR1 protein for the treatment of breast carcinoma in future.

Chemical depolymerization of recycled PET to oxadiazole and hydrazone derivatives: Synthesis, characterization, molecular docking and DFT study

The extensive use of polyethylene terephthalate (PET)-based packaging materials has increased the desire to focus on their recycling. In this study, a chemical depolymerization method is proposed for synthesizing terephthalic dihydrazide (TDH) via the aminolysis of post-consumed PET. TDH is further used as a precursor along with 2-chlorobenzoic acid and 4-hydroxybenzoic acid to synthesize aromatic compounds, such as two oxadiazole derivatives, with potential applications. TDH is also used along with 2-chlorobenzaldehyde, benzaldehyde, and 4-hydroxybenzaldehyde to synthesize three hydrazone derivatives. The five compounds (the oxadiazoles and hydrazones) are well characterized by ultraviolet–visible (UV–Vis) spectroscopy, elemental analysis, Fourier-transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR), scanning electron microscopy (SEM), and thermal analysis. The theoretical parameters of the compounds are studied by ab initio density functional theory (DFT). The DFT calculations are conducted at Becke’s three parameter and Lee–Yang–Parr (B3LYP) functional level of calculation with 631-G basis set. Moreover, several thermodynamic parameters at the ground state, such as the point group symmetry, dipole moment, and vibrational frequency, are calculated. The study of molecular docking of the synthesized compounds with target proteins (glucosamine-6-phosphate synthase (GlcN-6-P) and sterol 14α-demethylase (CYP51)) is conducted. Further, different parameters, such as the binding energy (BE), inhibition constant, internal energy, total intermolecular van der Waals forces, unbound energy, and hydrogen bond energy, are calculated. The three of the synthesized compounds are evaluated for antifungal and antibacterial activities using agar well diffusion method. The study of such compounds can offer a good prospective as potential antimicrobial and antifungal leads.

Self-Assembly of NaOL-DDA Mixtures in Aqueous Solution: A Molecular Dynamics Simulation Study.

The self-assembly behaviors of sodium oleate (NaOL), dodecylamine (DDA), and their mixtures in aqueous solution were systematically investigated by large-scale molecular dynamics simulations, respectively. The interaction mechanisms between the surfactants, as well as the surfactants and solvent, were revealed via the radial distribution function (RDF), cluster size, solvent-accessible surface area (SASA), hydrogen bond, and non-bond interaction energy. Results showed that the molecules more easily formed aggregates in mixed systems compared to pure systems, indicating higher surface activity. The SASA values of DDA and NaOL decreased significantly after mixing, indicating a tighter aggregation of the mixed surfactants. The RDF results indicated that DDA and NaOL strongly interacted with each other, especially in the mixed system with a 1:1 molar ratio. Compared to van der Waals interactions, electrostatic interactions between the surfactant molecules were the main contributors to the improved aggregation in the mixed systems. Besides, hydrogen bonds were found between NaOL and DDA in the mixed systems. Therefore, the aggregates in the mixed systems were much more compact in comparison with pure systems, which contributed to the reduction of the repulsive force between same molecules. These findings indicated that the mixed NaOL/DDA surfactants had a great potential in application of mineral flotation.

Deterioration of Kaihua handmade paper: Evolution of molecular, supermolecular and macroscopic structures

Valued for its toughness and durability, Kaihua paper has been famous in China since the Qing Dynasty. It attracts great attention on the extension of paper life. Understanding of the complex degradation behavior of handmade paper under various aging conditions is an essential precondition for preparing long-life handmade paper. However, it is still difficult to explain the reactions sequence of cellulose microstructure and its relationship with the macroscopic deterioration of handmade paper. Herein, different types of Kaihua handmade papers, produced by various raw materials and crafts, were artificially aged. The evolution of their multi-scale structures in dry-heat (DH) and wet-heat (WH) conditions was explored systematically. Two-dimensional correlation spectroscopy (2D-COS) distinguished possible carbonyl vibrations involving hydrolysis and oxidation of cellulose and gave sequential changes of various carbonyl groups, illustrating different evolutionary behaviors of molecular structure of papers in DH and WH aging process. The energy and distance of hydrogen bond, crystal size and microfiber accessibility were quantitatively calculated during the degradation of cellulose. In addition, correlations between microstructural evolution and macroscopic deterioration of handmade papers involving reduced mechanical properties and yellowing were revealed. The current results will help to establish a platform for the multi-scale detection of handmade paper and improve the understanding of the degradation mechanism of handmade paper under different reaction paths. It also provides useful foundation on the preparation of long-life paper and the conservation of paper-based culture relics.

Binding interaction of a potential statin with β-lactoglobulin: An in silico approach

This article reports the interaction between a synthetic statin, fluvastatin with bovine milk protein, β-lactoglobulin (BLG) through docking, constant pH molecular dynamics simulation (cpHMD) and binding free energy calculations. Docking provides the best fitted binding mode of the ligand with the receptor. We have carried out MD simulations of the protein and protein-ligand complex at two different pH viz. 7.0 and 1.5. We have found that the protein shows more compact behavior at pH 1.5 and this behavior is more prominent on complexation with the ligand. In support of this we have utilized the properties viz. root mean square deviations, root mean square fluctuations, radius of gyration, protein-ligand hydrogen bond and binding free energy calculations. Calculation of radius of gyration shows that the value decreases from 14.51 Å to 14.03 Å on complexation at pH 1.5. Calculations of hydrogen bonds at pH 1.5 confirms that hydrogen bonding interactions of the binding residues of the protein with the ligand provides stability to the complex. We have used molecular mechanics-generalized Born surface area (MMGBSA) method to estimate binding free energies of the protein with the ligand. MMGBSA calculations suggest that there is favorable binding interactions between the protein and the ligand with major contributions from Van der Waals interactions. We have found that the net average binding free energy is −29.394 kcal/mol that reveals a favorable binding interactions of BLG with the ligand. This study suggests that in spite of the acidic environment in the stomach BLG can act as a carrier for the acid-sensitive drug molecules such as fluvastatin because of its highly stable conformational behavior in the acidic pH.

Structural, spectroscopic, and in silico studies of 3-(dimethylamino)-1-(thiophen-2-yl)propan-1-ol: A potential antidepressant agent

The present study reports structural, spectroscopic signatures, reactivity parameters, and in silico anti-depressant activity of the title compound 3-(dimethylamino)-1-(thiophen-2-yl)propan-1-ol (DMATP). The structure of the DMATP compound has been unambiguously obtained through single crystal X-ray diffraction, vibrational spectroscopy, and thermal (TGA-DTA) analysis. DMATP is a chiral molecule containing a chiral methine carbon with S configuration and because of its chirality the compound crystallizes in the non-centrosymmetric orthorhombic P212121 space group. The thiophene ring and the attached nearly-planar side chain (excluding hydroxyl and one of the methyl group) are oriented to each other making a dihedral angle of 11.2(3)°. The –CH2CH2 bond at the center of the side chain has a staggered conformation. In the crystal structure, the molecules are linked via OH…N hydrogen bonds forming C(6) chains propagating along a-axis resulting in a one dimensional architecture. The intermolecular interactions were analysed qualitatively as well as quantitatively with the aid of 3D-Hirshfeld surface and 2D-fingerprint plot analysis. The optimization of the geometry of the DMATP molecule was performed at DFT/B3LYP/6–311G(d,p) basis set and showed good agreement with the experimental results. The assignment of each vibrational wavenumber was done according to potential energy distribution (PED) analysis. Furthermore, frontier molecular orbital analysis (FMO's), global reactivity parameters, nonlinear optical (NLO) properties, and nonbonding orbital (NBO) analysis were carried out by the same method. Local reactive properties of the title compound were explained by molecular electrostatic potential (MEP), and Fukui functions. The dissociation energies of hydrogen and other single bonds have been also estimated in order to understand the autoxidation mechanism and degradation properties. An anti-depressant study of the DMATP compound was carried out with human serotonin carriers (PDB ID: 5I73) and compiled a binding mechanism with standard anti-depressant drugs such as duloxetine, desvenlafaxine, and atomoxetine.

Relationships between Molecular Structure of Carbohydrates and Their Dynamic Hydration Shells Revealed by Terahertz Time-Domain Spectroscopy.

Despite more than a century of research on the hydration of biomolecules, the hydration of carbohydrates is insufficiently studied. An approach to studying dynamic hydration shells of carbohydrates in aqueous solutions based on terahertz time-domain spectroscopy assay is developed in the current work. Monosaccharides (glucose, galactose, galacturonic acid) and polysaccharides (dextran, amylopectin, polygalacturonic acid) solutions were studied. The contribution of the dissolved carbohydrates was subtracted from the measured dielectric permittivities of aqueous solutions based on the corresponding effective medium models. The obtained dielectric permittivities of the water phase were used to calculate the parameters describing intermolecular relaxation and oscillatory processes in water. It is established that all of the analyzed carbohydrates lead to the increase of the binding degree of water. Hydration shells of monosaccharides are characterized by elevated numbers of hydrogen bonds and their mean energies compared to undisturbed water, as well as by elevated numbers and the lifetime of free water molecules. The axial orientation of the OH(4) group of sugar facilitates a wider distribution of hydrogen bond energies in hydration shells compared to equatorial orientation. The presence of the carboxylic group affects water structure significantly. The hydration of polysaccharides is less apparent than that of monosaccharides, and it depends on the type of glycosidic bonds.